医学免疫学英文版教学课件：Chapter 20 Hypersensitivity

1、Chapter20 Hypersensitivity1Definition: when primed host touches the same antigen for the second time, appearing a harmful immune response that is heightened reactivity to this antigen, which causes tissue injury or functional disorder. 2Types of hypersensitivityType I: immediateType II:cytotoxicType

2、 III:Immune complexType IV:delayed-type1963, Gell and Coombs3Typehypersensitivity 1. Dominating features 2. Primary components 3. Process and mechanism 4. Common clinical disease 5. Measures of defense and therapy41. Features of Typehypersensitivity Also called allergy or anaphylaxisBe mediated by I

3、gE antibodyLocalized or systemic changesOccur and disappear rapidlyThe major problem is functional disorder almost without tissue injury Bear an individual difference and hereditary backgroundatopic individuals52. Components of Typehypersensitivity Antigen: Allergen IgE 6AllergenAllergen: something

4、a person is allergic to, induce IgE production selectively. Allergens can be to drugs, foods, plants, insects, and animals.7黑麦草 豚草属 猫尾草 桦树 水杨酸类 霉菌孢子 892. Components of a Typehypersensitivity Antigen: Allergen IgE Antibody: IgE1011122. Components of a Typehypersensitivity Antigen: Allergen IgE Antibo

5、dy: IgECells: Mast cells, basophils, eosinophils13 Mast cells, basophils, eosinophilsThe IgE produced by plasma cells binds to the Fc receptors located on mast cells, basophils or activated eosinophils. When an allergen crosslinks the IgE, the cell degranulates (releases the contents of its granules

6、). Histamine and other proteins that are released result in many of the allergic symptoms.1415162. Components of a Typehypersensitivity Antigen: Allergen IgE Antibody: IgECells: Mast cells, basophils, eosinophilsReceptor: FcR17IgE binding Fc receptors There are two kinds of IgE Fc receptors:FcR: hig

7、h affinityFcR (CD23): low affinity18193. Process and mechanism Sensitization phase -primed mast cell Excitation phase -mast cell activation -mediator production Effector phase20Sensitization phase Allergen Production of IgE IgE binds to FcR I on mast cells Primed mast cells21Plasma CellMast cell gra

8、nulesFcRI IgE22 IgE23 IgEFcRIMast cell Primed mast cell24 Excitation phase Allergen binding to IgE cross-links FcR molecules on the mast cellsinduces the release of mediators (degranulation) restored mediators new synthesized mediators (histamine) (leukotrienes) 25Sensitization against allergenspoll

9、en2627The activators of mast cells28Allergen29DegranulationHistamineProteasesHeparinChemotactic factors for neutrophils and eosinophilsImmediate responseoccurs within minutes30Mast cell activation products-Preformed mediatorsHistamine: vascular permeability, vasodilatationconstriction of intestinal

10、and bronchial smooth musclemucus secretionpruritus 31Activated Mast cellLeukotrienesProstaglandin D2PAFCytokines(IL-4, TNF-)Late phase response occurs within hours.32Mast cell activation products-Newly formed mediatorsLeukotriene C4 & D4: strong constriction of bronchial smooth muscle, mucus secreti

11、on, vascular permeability, vasodilatation.3334Effector phaseThe effect of mediators: Increase vascular permeability, vasodilatation Promote bronchial and visceral smooth muscle contraction Increase secretion of glands 35Immediate phase reaction: occurs within minutes , mainly caused by histamine， co

12、nstriction of smooth muscle, vascular permeability.Late phase reaction: occurs within hours, caused by the induced synthesis and release of mediators including LT, PAF. 36374. Common diseases caused by type I hypersensitivityHypersensitivity in respiratory tract： allergic rhinitisHypersensitivity in

13、 skin: Hypersensitivity in gastrointestinal tract： Systemic allergy: 383940414. Common diseases caused by type I hypersensitivityHypersensitivity in respiratory tract: allergic rhinitis，allergic asthmaHypersensitivity in skin:Hypersensitivity in gastrointestinal tract: Systemic allergy: 4243444. Com

14、mon diseases caused by type I hypersensitivityHypersensitivity in respiratory tract: allergic rhinitis，allergic asthmaHypersensitivity in skin: urticaria，eczemaHypersensitivity in gastrointestinal tract: Systemic allergy: 45Many organs are be affected by “allergy” The skinUrticaria(hives)Wheal and f

15、lare reaction46Many organs are be affected by “allergy” The skineczema474. Common diseases caused by type I hypersensitivityHypersensitivity in respiratory tract: allergic rhinitis，allergic asthmaHypersensitivity in skin: urticaria，eczemaHypersensitivity in gastrointestinal tract: food allergiesSyst

16、emic allergy: 48494. Common diseases caused by type I hypersensitivityHypersensitivity in respiratory tract: allergic rhinitis，allergic asthmaHypersensitivity in skin: urticaria，eczemaHypersensitivity in gastrointestinal tract: food allergiesSystemic allergy: anaphylactic shock-drug, serum50 5.Measu

17、res of defense and therapySkin test: find allergen5152 5.Measures of defense and therapySkin test: find allergenDesensitization: reducing the quantity of IgE present in the individualHyposensitization: from IgE to IgG53Hyposensitization54 5.Measures of defense and therapySkin test: find allergenDese

18、nsitization: reducing the quantity of IgE present in the individualHyposensitization: from IgE to IgGAnti-allergic drugs:to block the production or release of mediators or to antagonize mediator actions on target cellsImmunotherapy55Type hypersensitivity 1. Dominating features 2. Primary components

19、3. Process and mechanism 4. Common clinical diseases561. Dominating features Also called cytotoxic hypersensitivity Ag is on the surface of cell Ab is IgG or IgM Complements, macrophage, NK cells participate in Cell lysis or tissue injury572. Components of a Type hypersensitivity Antigen: on the sur

20、face of target cellAntibody: IgM, IgGCells: macrophage, neutrophil, NKReceptor: FcRComplements58 3.Mechanism of type II hypersensitivity Ab is induced by the Ag-IgM, IgG Binding of the antigen on cells by the corresponding antibody can cause activation of complements-MAC Opsonization of phagocytosis

21、 (C3b, Ab) ADCC Actions of C3a, C5a5960Type II hypersensitivity mechanism61624. The diseases caused by Type II hypersensitivityTransfusion Reactions63Transfusion ReactionsABO blood group antigens stimulate a type II response.Usually the antibody produced is IgM.Typing the blood before a transfusion

22、prevents this reaction644. The diseases caused by Type II hypersensitivityTransfusion ReactionsNeonate hemolysis(Rh blood group antigen)65Hemolytic Disease of the NewbornMaternal IgG specific for the fetal blood groups crosses the placenta and destroys the fetal red blood cells6667684. The diseases

23、caused by Type II hypersensitivityTransfusion ReactionsNeonate hemolysis(Rh blood group antigen)Autoimmune hemolytic anemiaDrug reactions- hemolytic anemia, thrombocytopenic purpura, granulocytopenia69Drug-Induced hemolytic anemiaSome antibiotics (penicillin, cephalosporin and streptomycin) stick no

24、nspecifically to proteins on red blood cells.An antibody response can develop to the drug/protein complex.Lysis of the red blood cells causes anemia.70Drug reaction-hemolytic anemia714. The diseases caused by Type II hypersensitivityTransfusion ReactionsNeonate hemolysis(Rh blood group antigen)Autoi

25、mmune hemolytic anemiaDrug reactions- hemolytic anemia, thrombocytopenic purpura, granulocytopeniaGraves disease72Type hypersensitivity 1. Dominating features 2. Primary components 3. Process and mechanism 4. Common clinical diseases731. Dominating featuresAlso called Immune complex mediated hyperse

26、nsitivityAntigen is soluble Antibody is IgG or IgMImmune complex disease 742. Components of a Type hypersensitivity Antigen: solubleAntibody: IgM, IgGComplementsCells: basophil, mast cell, neutrophil, platelets75Ag+AbImmune complex,ICLarge ICPhagocytosis by phagocytesSmall ICDischarged from circulat

27、ionMedium ICExist in circulation, and deposit3.Mechanism of type hypersensitivityFormation of medium immune complex76Deposition of the medium IC on basement membrane Complements: are activated by the IC, producing C3a and C5a, which mediate an local inflammation by activating mast cells and basophil

28、s and recruiting neutrophils-edema. Neutrophils: release enzymes-tissue injury. Platelets: ischemia, necrosis.77Type III hypersensitivity mechanism784. Diseases caused by type III hypersensitivityLocalized diseases: Arthus reaction Arthus like reaction, farmers lungSysmetic diseases: serum sickness

29、79Serum sickness804. Diseases caused by type III hypersensitivityLocalized diseases: Arthus reaction Arthus like reaction, farmers lungSysmetic diseases: serum sickness poststreptococcal glomerulonephritis rheumatoid arthritis systemic lupus erythematosus 81Systemic lupus erythematosus82Typehypersen

30、sitivity 1. Dominating features 2. Primary components 3. Process and mechanism 4. Common clinical diseases831. Dominating featuresA hypersensitivity reaction mediated by specific T cells (Th1)Delayed reaction: arises more than a day after encounter with the same antigen and reaches top reaction in 4

31、8-72 hrPathological change is an inflammation characterized by infiltration of macrophage and lymphocyteNo antibody and complement attend842. Components of a Type hypersensitivity AntigenAntibody: noComplements: noCells: T cells, macrophages853.Mechanism of type IV hypersensitivity Formation of sens

32、itized Th1. The same antigen is presented by DC to elicit the secondary response, in which the effector Th1 activates the macrophage to induce an inflammation characterized by infiltration of macrophages and lymphocytes. CTL induced cytotoxicity.86874. Diseases caused by TypeIV hypersensitivityInfectious DTH: Granulomatous disease, OT test88Granuloma in a leprosy patient89Th 1细胞多核巨大细胞巨噬细胞上皮样细胞细菌纤维母细胞慢 性 肉 芽 肿904. Disease